ELECTROSTATIC SURFACE OPTIMIZATION FOR OSSEOINTEGRATION

用于骨整合的静电表面优化

• 批准号: 6171196
• 负责人: MICHELE S MARCOLONGO
• 金额: $ 7.5万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6171196
• 关键词: atomic force microscopy; biomaterial development /preparation; biomaterial evaluation; biomaterial interface interaction; biomaterials; cell adhesion; conformation; fibronectins; fluorimetry; ionic bond; molecular film; osteoblasts; surface property; tissue /cell culture; tissue engineering; titanium

Debilitating degenerative joint diseases are routinely treated by joint replacements to allow restoration of relatively pain-free motion to the affected joint. Fracture healing and bony fusion (for example, in the treatment of degenerative disease) can be facilitated by the use of synthetic bone grafts or tissue engineered scaffolds. The success of each of these surgical interventions is dependent on the ability of bone tissue to integrate with the surface of the implant biomaterial. In order to achieve osseointegration, the bone forming cell (the osteoblast) must first adhere to the biomaterial surface; the osteoblast/biomaterial interaction must then be conducive to the elaboration of a bone-specific extracellular matrix (ECM) which will undergo mineralization and remodeling to form an integrated bone/biomaterial interface. A handful of synthetic biomaterials, termed bioactive materials, will elicit osseointegration; these are calcium phosphate ceramics (including hydroxyapatite) and bioactive glasses. In contrast, the more commonly used bone implant materials, titanium alloy (Ti6A14V) and cobalt chromium alloy, will not support osteoblast adhesion and direct bone bonding in vivo, instead the resulting interface consists predominantly of fibrous tissue. From many experiments it is clear that material properties affecting osseointegration include surface charge, chemistry, and topography, although the specific parameters that facilitate osseointegration are presently poorly understood. Once the specific surface properties which encourage osteoblast attachment are determined, it would then be possible to engineer the surface of any compatible material to make that material bioactive or bone bonding. We suggest that a dominant mechanism in cellular attachment to a biomaterial surface is electrostatic in nature, with the electrostatic characteristics of the surface encouraging the adsorption of specific ECM proteins (in particular, fibronectin, an important serum protein involved in cell adhesion) to facilitate initial attachment of osteoblasts to the biomaterial surface. While evidence of the importance of electrostatic interactions has been documented, the relative contributions of surface charge, charge distribution, and charge density on cellular attachment and protein adsorption are presently not understood. Previous studies have been limited in this regard as they have not uncoupled the electrostatics from functionality and surface energy due to surface chemistry. In this work, we propose a unique model to elucidate the effect of electrostatics on osteoblast adhesion and protein adsorption. We hypothesize that negatively charged surfaces will promote osteoblast attachment and spreading, while positively charged surfaces will inhibit cellular attachment and we expect that osteoblasts will exhibit differential adhesion on surfaces whose charge distribution and charge density has been patterned at varying subcellular dimensions. Further, we hypothesize that the quantity of fibronectin adsorbed to differently charged surfaces will not differ, but the conformation of the fibronectin on those charged surfaces will.

衰弱退行性关节病的常规治疗方法是关节。 替换以允许恢复相对无痛的运动到 受影响的关节。骨折愈合和骨融合(例如，在 退行性疾病的治疗)可以通过使用 人工骨移植或组织工程支架。的成功之处 每一种外科治疗都依赖于骨骼的能力。 组织与植入物生物材料的表面结合。 为了实现骨整合，骨形成细胞(骨形成细胞) 成骨细胞)必须首先附着在生物材料表面； 成骨细胞/生物材料的相互作用必须有利于 研制一种骨特异性细胞外基质(ECM)，将 经历矿化和改造，形成完整的 骨/生物材料界面。几种合成生物材料，被称为 生物活性材料，将诱导骨整合；这些是钙 磷酸盐陶瓷(包括羟基磷灰石)和生物活性玻璃。 相比之下，更常用的骨植入材料钛 合金(Ti6A14V)和钴铬合金不支持成骨细胞 体内的粘连和直接骨结合，而不是结果 界面主要由纤维组织组成。从许多人 实验表明，影响材料性能的因素 骨整合包括表面电荷、化学和地形， 尽管促进骨整合的具体参数是 目前人们对此知之甚少。一旦特定的表面属性 鼓励成骨细胞附着是确定的，那么它就会 有可能设计出任何兼容材料的表面来制造 材料生物活性或骨结合。 我们认为，细胞依附于一种 生物材料表面在性质上是静电的，具有静电 鼓励吸附特定物质的表面特性 细胞外基质蛋白(尤其是纤维连接蛋白，一种重要的血清蛋白 参与细胞黏附)以促进初始附着 成骨细胞生长到生物材料表面。虽然有证据表明 静电相互作用的重要性已经被记录在案， 表面电荷的相对贡献、电荷分布和 细胞附着和蛋白质吸附的电荷密度是 目前还不清楚。以往的研究仅限于此。 认为它们没有将静电从功能中分离出来 以及表面化学产生的表面能。在这项工作中，我们建议 一种解释静电对成骨细胞影响的独特模型 粘附性和蛋白质吸附。我们假设带负电荷 表面会促进成骨细胞的附着和扩散，而 带正电的表面会抑制细胞附着，我们 预计成骨细胞将在表面表现出不同的黏附 其电荷分布和电荷密度已被图案化 不同的亚细胞维度。此外，我们假设 吸附在不同电荷表面的纤维连接蛋白的量将 没有区别，但带电的人身上的纤维连接蛋白的构象 曲面将会。